ALIMENTARY TRACT:CLINICAL RESEARCH Frequency of HFE Mutations Among Turkish Blood Donors According to Transferrin Saturation Genotype Screening for Hereditary Hemochromatosis Among Voluntary Blood Donors in Turkey Halis Simsek, MD,* Hale Sumer, MD,† Engin Yilmaz, MD,‡ Yasemin H. Balaban, MD,* Osman Ozcebe, MD,§ Gulsen Hascelik, MD,¶ Yahya Buyukasık, MD,§ and Gonca Tatar, MD* Background and Goals: The C282Y and H63D mutations of HFE gene are associated with hereditary hemochomatosis (HH), the most common autosomal recessive disorder in European population. This is the first Turkish population study of, the prevalence of these muta- tions. Study: 2677 healthy volunteer blood donors were screened by means of transferrin saturation (TS) with the cutoff value of 45. As study group, 86 donors with a TS 45 or higher and as control group 57 donors with TS less than 45 were tested for these mutations, ferritin, and alanin aminotransferase (ALT) levels. Results: The mean age of donors were 33 ± 9 and 94.1% of them were male. The number of donors with TS 45 or higher was 265 (9.9%). C282Y mutation was not detected. The frequency of H63D mutation in the study, control and general groups were 27.32%, 21.05%, and 24.83%, respectively. As a result, the H63D mutation was present in 60 out of 143 participants in whom 49 were heterozy- gote (frequency of heterozygote allel 49/286 = 17.13%), 11 were ho- mozygote (frequency of homozygote allel 22/286 = 7.69%). Serum ALT and TS were not affected from the type of H63D mutation. There was no difference in ferritin levels according to type of H63D muta- tions among 143 blood donors. Conclusion: This study revealed the absence of C282Y mutation in our population. Although the frequency of H63D heterozygosity seems to be higher than the other population, the genetic screening for the HFE gene mutation is inadequate and the phenotypic screening with TS and ferritin seems to be preferable in Turkish population. Key Words: hemochromatosis, screening, HFE, mutation, H63D, C282Y (J Clin Gastroenterol 2004;38:671–675) H ereditary hemochromatosis (HH) is the most common au- tosomal recessive disorder in populations of European origin, affecting approximately 1:200–400 individuals. 1,2 The abnormally high iron absorption from the intestine leads to ex- cessive iron accumulation in the liver and other organs and as a result, cellular damage and fibrosis occur. With early detec- tion of the disease and by initiating phlebotomy, complications of HH; such as cirrhosis, hepatocellular carcinoma, arthropa- thy, diabetes, and other endocrinopathies, can be prevented. 3,4 Among the 37 allelic variants of HFE described, 2 mutations, C282Y and H63D, are significantly correlated with clinically manifested HH. The homozygote C282Y mutation is present in 69% to 100% of HH patients depending on the population. 5– 10 The role of HFE gene product is to interact with the trans- ferrin receptor, TfR, at the plasma membrane and to reduce the affinity of TfR for iron bounded transferrin by 5- to10-fold. 11– 14 The C282Y mutant gene product has the altered structure that fails to associate with B 2 microglobulin. The mutant HFE protein leads to disturbed expression of the HFE-B 2 micro- globulin complex on the cell surface so that the complex can- not interact with TfR nor reduce the affinity of TfR for trans- ferrin. 11,15 On the other hand, the H63D mutation seems to neither disturb B 2 microglobulin association with HFE protein nor the expression of HFE protein on the cell surface. It also decreases the affinity of TfR for transferrin to a much lesser extent than the wild type HFE protein. 11 From population studies involving numerous countries, it has been calculated that the overall frequency of the gene allele for C282Y mutation in North America and northern Eu- rope is 6.8% and for H63D mutation is 17.6%. 11 The C282Y mutation is most frequent in northern to western Europe, but Received for publication August 6, 2003; accepted October 15, 2003. From the *Unit of Gastroenterology, Hacettepe University, Ankara, Turkey; the †Department of Internal Medicine, Hacettepe University, Ankara, Tur- key; the ‡Department of Medical Biology, Hacettepe University, Ankara, Turkey; the §Unit of Hematology, Hacettepe University, Ankara, Turkey; and the ¶Unit of University Microbiology and Clinical Microbiology, Hacettepe University, Ankara, Turkey. Presented at DDW, San Francisco, California, May 2002. The study was supported by Hacettepe University Research Center. Reprints: Halis Simsek, MD Cinnah Caddesi No:110/3 Çankaya/Ankara/Turkey (e-mail: hsimsek@hacettepe.edu.tr). Copyright © 2004 by Lippincott Williams & Wilkins J Clin Gastroenterol • Volume 38, Number 8, September 2004 671